Cancer stem cells and strategies for targeted drug delivery
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REVIEW ARTICLE
Cancer stem cells and strategies for targeted drug delivery Jin Cao1,2 · Shubhmita Bhatnagar2,3 · Jiawei Wang2,5 · Xueyong Qi1 · Swayam Prabha2,4 · Jayanth Panyam2,3 Accepted: 1 October 2020 © Controlled Release Society 2020
Abstract Cancer stem cells (CSCs) are a small proportion of cancer cells with high tumorigenic activity, self-renewal ability, and multilineage differentiation potential. Standard anti-tumor therapies including conventional chemotherapy, radiation therapy, and molecularly targeted therapies are not effective against CSCs, and often lead to enrichment of CSCs that can result in tumor relapse. Therefore, it is hypothesized that targeting CSCs is key to increasing the efficacy of cancer therapies. In this review, CSC properties including CSC markers, their role in tumor growth, invasiveness, metastasis, and drug resistance, as well as CSC microenvironment are discussed. Further, CSC-targeted strategies including the use of targeted drug delivery systems are examined. Keywords Cancer stem cells (CSCs) · Drug delivery system · Anti-tumor therapy · Drug-resistance · Cancer biology
Introduction Stem cells are specialized cells that possess the ability to differentiate into varied cell types. In a tumor, all tumor cells are not alike; some tumor cells possess greater differentiation capabilities than others. The notion that tumors have stem cells—cancer stem cells (CSCs)—has stirred a lot of scientific interest and greatly changed how we think about treating cancer. These self-sustaining stem cells possess characteristic self-renewal ability, enabling them to give rise to heterogenous tumor lineages. Since these cells are capable of forming an entire tumor, they are also called †
Jin Cao and Shubhmita Bhatnagar contributed equally to this manuscript * Jayanth Panyam [email protected] 1
School of Pharmacy, Jiangsu University, Zhenjiang 212013, Jiangsu, China
2
College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA
3
School of Pharmacy, Temple University, Philadelphia, PA 19140, USA
4
Cancer Research & Molecular Biology and Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
5
College of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA
tumor-initiating cells (TICs). The TICs differentiate into progenitor cells and further into other kinds of cells found in the tumor. Two models have been used to describe the origin of CSCs. The stochastic model (Fig. 1) envisages that every tumor cell has a low but equal chance of limitless proliferation, behaving as a stem cell. As naturally acquired cell mutations are selected over time, the most aggressive tumor cell populations are selected. These populations are responsible for tumor progression and maintenance. The hierarchal model, on the other hand, proposes that only a distinct subset of tumor cells possess the potential of limitless proliferation. These cells possess the ability of self-renewal and form the top of the tumor pyr
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